Discovering hematoma-stimulated circuits for secondary brain injury after intraventricular hemorrhage by spatial transcriptome analysis

Abstract

IntroductionCentral nervous system (CNS) diseases, such as neurodegenerative disorders and brain diseases caused by acute injuries, are important, yet challenging to study due to disease lesion locations and other complexities.MethodsUtilizing the powerful method of spatial transcriptome analysis together with novel algorithms we developed for the study, we report here for the first time a 3D trajectory map of gene expression changes in the brain following acute neural injury using a mouse model of intraventricular hemorrhage (IVH). IVH is a common and representative complication after various acute brain injuries with severe mortality and mobility implications.ResultsOur data identified three main 3D global pseudospace-time trajectory bundles that represent the main neural circuits from the lateral ventricle to the hippocampus and primary cortex affected by experimental IVH stimulation. Further analysis indicated a rapid response in the primary cortex, as well as a direct and integrated effect on the hippocampus after IVH stimulation.DiscussionThese results are informative for understanding the pathophysiological changes, including the spatial and temporal patterns of gene expression changes, in IVH patients after acute brain injury, strategizing more effective clinical management regimens, and developing novel bioinformatics strategies for the study of other CNS diseases. The algorithm strategies used in this study are searchable via a web service (www.combio-lezhang.online/3dstivh/home).

Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality

“…The genes predictive of signal quality in this study should be explored further to confirm their generalizability as biomarkers of signal quality: many experimental factors could influence results. It is important to contextualize the results of our analysis with several considerations, including: (1) our recording metrics may not capture all aspects of quality relevant to the variety of device applications in use, (2) relatively low sample size (although, our sample sizes are aligned with reports in literature using ST assays [21,[47][48][49]) and (3) the potential to over-interpret causation when assessing the results of regression.…”

“…but the result did not reach statistical significance (p > 0.05), likely due to the relatively limited number of samples probed per time point. ST yields a high quantity of information per sample for the expression of thousands of genes, but typically, relatively few samples are assessed due to associated costs [21,[47][48][49]. However, evidence of neuronal damage/loss is supported by a reduction in the expression of the neuron-specific Snap25 gene (figure 2).…”

CpG Island Definition and Methylation Mapping of the T2T-YAO Genome

“…However, there is currently no such web service that collects and manages CGI and methylation annotation data for the Chinese T2T genome. Therefore, we will build a web service for online computation, data sharing and visualization based on high-performance computing[33, 34], such as GPU acceleration and distributed computing, to provide a data foundation and an online platform for further study.…”

A promising self-nanoemulsifying adjuvant with plant-derived saponin D boosts immune response and exerts an anti-tumor effect

“…BALB/c mice and C57BL/6 mice (SPF, female, 6–8 weeks of age) were purchased from Beijing HFK Bioscience and Hunan SJA Laboratory Animal Co. (China), respectively. The animal experimental protocols were approved by the Laboratory Animal Welfare and Ethics Committee of the Third Military Medical University and performed according to the Guide for the Care and Use of Laboratory Animals ( 27 ); professional technicians, skilled operation of equipment, and suitable experimental conditions for the animals were ensured in order to minimize pain experienced by the mice.…”

“…The animal experimental protocols were approved by the Laboratory Animal Welfare and Ethics Committee of the Third Military Medical University and performed according to the Guide for the Care and Use of Laboratory Animals ( 27 ).…”